This is a new program project with the aim of uncovering the basic principles of cellular and chemical organization, development and modifiability of primate neocortex. A team of investigators with experience in cell biology, biochemistry, immunocytochemistry electronmicroscopy, endocrinology, pharmacology, psychobiology, computer engineering, veterinary medicine, neurosurgery and neuropathology have joined forces to explore (1) determinants of laminar and areal positions and differentiation of cell phenotypes; (2) establishment of extrinsic and intrinsic axonal connections and synaptogenetic sequences; (3) regional development of putative transmitters and their receptors; (4) emergence and regional distribution of steriod hormone receptors; and (5) emergence of normal and abnormal functions. Each specific aim will consist of a series of interrelated experiments on developing rhesus monkeys using a battery of the most advanced neurobiological techniques each requiring participation of several investigators. The design of the projects allows use of each animal for multiple experiments. The techniques of prenatal neurosurgery on temporarily exteriorized fetuses that were refined in our department enable experimental manipulation of cortical development that will for the first time allow exploration of various epigenetic factors and mechanisms that govern organization and parcellation of primate neocortex. All studies will be done on the rhesus monkey with the conviction that the results may aid the understanding of mechanisms of normal cortical development as well as pathogenesis of developmental disorders affecting higher cortical functions in humans. It is expected that this program will: 1) promote interaction and collaboration by investigators with various scientific backgrounds; 2) support core facilities for sophisticated computer data and graphic analyses, and breeding of timed pregnancies in rhesus monkeys; and 3) stimulate sharing of ideas, equipment, know how and valuable primate tissue.